DNA Nanotechnology: building programmable materials and nanometer-scale devices
Previous and Current Research
Synthetic polymer materials have revolutionized the world within the last century. Yet, a glance at nature reveals, how limited the functions of synthetic polymers still are in comparison to biological matter: biological cells use molecular self-assembly and self-organization to build complex materials (e.g. the cytoskeleton) and to operate sophisticated macromolecular devices (e.g. motor proteins). For many years, chemists and material scientists have been intrigued by one question: How can we construct materials with equally sophisticated and versatile features?
Inspired by biology’s refined design principles, our group strives to develop materials with programmable and reconfigurable properties. We use DNA as the quintessential component for these materials: aside from its crucial role as the carrier of genetic information, DNA can be used as a construction material to assemble artificial nanometer-scale structures. This research field at the interface of science and engineering is known as DNA Nanotechnology.
By combining concepts of DNA Nanotechnology with traditional polymer chemistry and molecular biology, we aim to transfer the programmability and reconfigurability of nanometer-scale DNA devices to the macroscopic level. To this end, structural scaffolds of synthetic acryloyl polymers are endowed with DNA-based nanomodules via non-covalent self-assembly (see Figure). The ultimate target is the development of new classes of materials that can be programmed to perform complex tasks for diverse biomedical applications (see Future projects and goals).
During my postdoctoral studies, we have developed SNAPCAR, a method for scalable isolation of kilobase-long single-stranded DNA (Krieg & Shih, Angew. Chem. Int. Ed., 2018). This technology enables construction of new types of DNA origami structures and better repair templates for CRISPR/Cas9 gene editing. Based on SNAPCAR, our team has recently developed a stimuli-responsive polymer that facilitates rapid pulldown and release of DNA targets (Krieg et al. bioRxiv, 2019). This new pulldown method was used to enhance the data quality – and thus the diagnostic value – of expression profiles that were obtained from clinical cDNA libraries. Moreover, we explore the potential of DNA origami structures for assembling molecular machines, capable of performing complex operations that cannot be achieved by currently existing molecular biology tools.
Future Projects and Goals
Our future research will focus on the development of three application areas, emerging from a single programmable material platform (see Figure):
- Materials for purification and labeling of DNA and RNA libraries will increase the efficiency and sensitivity of new diagnostic assays that rely on Next-Generation Sequencing.
- Printable and dynamically reconfigurable 3D cell culture matrices will be used to generate better in-vitro models of healthy and damaged tissues.
- The point-of-care detection of pathogen-specific nucleic acids will be achieved by materials that sensitively respond to DNA-based reaction networks.
Methodological and Technical Expertise
- DNA Nanotechnology (sequence design, assembly, DNA origami)
- Organic, supramolecular and polymer chemistry
- Standard methods in molecular biology
- Nanoparticle synthesis and purification
- Nanomaterial characterization: electron microscopy, atomic force microscopy, and oscillatory rheology
Krieg E*, Gupta K, Dahl A, Lesche M, Boye S, Lederer A, Shih WM*
A smart polymer for sequence-selective binding, pulldown and release of DNA targets.
bioRxiv, 573030 (2019)
Krieg E, Shih WM
Selective nascent polymer catch-and-release enables scalable isolation of multi-kilobase single-stranded DNA.
Angew Chem Int Ed, 57, 714–718 (2018)
Krieg E*, Bastings MMC, Besenius P*, Rybtchinski B*
Supramolecular polymers in aqueous media.
Chem Rev, 116, 2414–2477 (2016)
Krieg E, Weissman H, Shimoni E, Shirman E, Rybtchinski B
A recyclable supramolecular membrane for size-selective separation of nanoparticles.
Nature Nanotech, 6, 141–146 (2011)
Krieg E, Shirman E, Weissman H, Shimoni E, Wolf S, Pinkas I, Rybtchinski B
Supramolecular gel based on a perylene diimide dye: multiple stimuli responsiveness, robustness, and photofunction.
J Am Chem Soc, 131, 14365–14373 (2009)
*shared corresponding authorship